By immunizing and boosting rabbits with phenol-inactivated S. aureus and challenging them topically with viable S. aureus, we have established a rabbit model for vascularized, elevated nodular infiltrates of the cornea resembling phlyctenules in humans and peripheral corneal infiltrates running parallel to the limbus and separated from it by a lucid interval resembling catarrhal infiltrates in humans. Immunopathological studies of antibodies and complement deposition in these lesions will be correlated with their histopathology. We plan to determine the role of an intact corneal epithelium as a barrier between staphylococcal antigens in the tear film and antibody in the corneal stroma and to determine if rabbits can be immunized to S. aureus through the ocular route without systemic immunization with complete Freund's adjuvant since this would most closely resemble the human predicament. We will determine the importance of various strains of staphylococci and the factors they produce and the role of specific staphylococcal antigens such as protein A, ribitol teichoic acid and peptidoglycan in the production of these hypersensitivity lesions of the cornea. Rabbits immunized and challenged with various staphylococcal strains and antigens will be studied for evidence of cell-mediated immunity to protein A, ribitol teichoic acid, peptidoglycan and sonicated suspensions of various staphylococcal strains by means of the lymphocyte stimulation assay and the leucocyte migration inhibition assay. In addition, antibody titers to these antigens will be determined double diffusion in agar gel. In this way, the development and progression of corneal lesions can be correlated with antibody levels and cell-mediated immunity to various strains of S. aureus and their antigens. We plan to extend our model to include mice. Athymic mice will be used to assess the importance of T lymphocytes, and mice with absolute deficiencies of either C4 or C5 will be used to determine the importance of complement in the immunopathogenesis of these lesions. With regard to humans, we plan to determine if there is an increased prevalence of a particular phage type in patients with phlyctenules and catarrhal infiltrates or ulcers and the relative importance of humoral and cell-mediated immunity to various staphylococcal antigens in the pathogenesis of these corneal lesions.